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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuroprotection of catalpol and its mechanism was evaluated in cerebral ischemic model in gerbils. Three groups were designed as sham-operated, ischemia-treated, respectively, with catalpol and saline. Catalpol was injected intraperitoneally immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h with the dose of 5.0 mg/kg. The neuroprotection was estimated by the indexes of behavior and histology. Behavioral testing was performed in Y-maze and the survival neurons in CA1 subfield were counted under a microscope after behavioral testing. In addition, apoptosis induced by ischemia was also examined by using the terminal deoxynucleotidyl transferase-mediated UTP nick end labeling method. It was shown that catalpol significantly attenuated apoptosis, rescued hippocampal CA1 neurons and reduced cognitive impairment. In order to make clear the mechanism of catalpol's neuroprotection, the activities of endogenous antioxidants and nitric oxide synthase together with the content of lipid peroxide in cortex and hippocampus were assayed. The results proved that catalpol significantly reduced the content of lipid peroxide, increased the activity of glutathione peroxidase and decreased the activity of nitric oxide synthase. All these suggested that catalpol was a potential neuroprotective agent and its neuroprotective effects were achieved at least partly by promoting endogenous antioxidant enzymatic activities and reducing the formation of nitric oxide.
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PMID:Neuroprotection of catalpol in transient global ischemia in gerbils. 1538 Mar 24

Recent studies suggest that postmitotic neurons can reenter the cell cycle as a prelude to apoptosis after brain injury. However, most dying neurons do not pass the G1/S-phase checkpoint to resume DNA synthesis. The specific factors that trigger abortive DNA synthesis are not characterized. Here we show that the combination of hypoxia and ischemia induces adult rodent neurons to resume DNA synthesis as indicated by incorporation of bromodeoxyuridine (BrdU) and expression of G1/S-phase cell cycle transition markers. After hypoxia-ischemia, the majority of BrdU- and neuronal nuclei (NeuN)-immunoreactive cells are also terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-stained, suggesting that they undergo apoptosis. BrdU+ neurons, labeled shortly after hypoxia-ischemia, persist for >5 d but eventually disappear by 28 d. Before disappearing, these BrdU+/NeuN+/TUNEL+ neurons express the proliferating cell marker Ki67, lose the G1-phase cyclin-dependent kinase (CDK) inhibitors p16INK4 and p27Kip1 and show induction of the late G1/S-phase CDK2 activity and phosphorylation of the retinoblastoma protein. This contrasts to kainic acid excitotoxicity and traumatic brain injury, which produce TUNEL-positive neurons without evidence of DNA synthesis or G1/S-phase cell cycle transition. These findings suggest that hypoxia-ischemia triggers neurons to reenter the cell cycle and resume apoptosis-associated DNA synthesis in brain. Our data also suggest that the demonstration of neurogenesis after brain injury requires not only BrdU uptake and mature neuronal markers but also evidence showing absence of apoptotic markers. Manipulating the aberrant apoptosis-associated DNA synthesis that occurs with hypoxia-ischemia and perhaps neurodegenerative diseases could promote neuronal survival and neurogenesis.
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PMID:Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain. 1556 94

Occlusion of coronary artery causes cardiomyocyte dysfunction. Reperfusion relieves ischemia by providing cells with metabolites and oxygen, thereby preventing extensive tissue damage. Although reperfusion salvages the myocardium, it also initiates a series of events including myocardial apoptosis and necrosis. The common inducers of apoptosis include reactive oxygen species (ROS). Caffeic acid phenethyl ester (CAPE) is known as an antioxidative, anti-inflammatory effects, may protect myocardial ischemia-reperfusion (MI/R)-induced apoptosis. We have previously reported that CAPE reduced MI/R-induced necrosis. Therefore, this study was focused to investigate protective effect of CAPE on the distinct form of cell death; apoptosis in an in vivo rat model. To produce MI/R, a branch of the descending left coronary artery was occluded for 30 min followed by 2 h reperfusion. ECG changes, blood pressure (BP), and heart rate (HR) were measured before occlusion and continued both occlusion and reperfusion. CAPE (50 micromol/kg) was given 10 min before ischemia via jugular vein. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated d UTP-biotin nick and labeling (TUNEL) method. Also, cysteine aspartate specific proteinase (caspase)-3 and caspase-9 activities a universal effector of apoptosis, were determined. Trunk blood was extracted to determine the serum contents related to oxidant-antioxidant status. In hemodynamic parameters, there was no significant difference in HR or BP values among any group. CAPE administration had no a significant effect on hemodynamic parameters during ischemia or reperfusion. Control group revealed extensive TUNEL-positive cardiomyocytes especially in free wall of left ventricule, interventiculare septum and nearly apex zone. Intensity of TUNEL-positive cardiomyocytes reduced as a result of CAPE treatment compared to control group in the same sections. Result of the caspase activities was found to correlate with TUNEL evaluation. CAPE also, ameliorated antioxidant status. We propose that CAPE acts in the heart as a potent scavenger of free radicals to prevent the apoptotic effect of I/R. Further studies are needed to elucidate the mechanisms of apoptotic death machinery.
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PMID:Protective effect of caffeic acid phenethyl ester (CAPE) on myocardial ischemia-reperfusion-induced apoptotic cell death. 1572 9

Hypertension and sodium retention are features of a diminished 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). The activity of this enzyme is reduced in various disease states with abnormal renal sodium retention and hypertension, including preeclampsia. ATP release to the extracellular compartment is observed with shear stress, inflammation, and placental ischemia. It was hypothesized that ATP downregulates 11beta-HSD2 activity. For that purpose, cell lines from different tissues that previously were used to study the regulation of 11beta-HSD2 were investigated: JEG-3, a vascular trophoblastic; LLCPK1, a renal tubular; and SW620, a colonic epithelial cell line. The 11beta-HSD2 activity, assessed by the conversion of 3H-cortisol to cortisone, was reversibly reduced during incubation with ATP or its stable analogue ATPgammaS in intact JEG-3 and LLCPK1, but not in SW620 cells. In JEG-3 cells, the purinergic antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid but not suramin reversed the inhibition. Incubation with UTP and ADP and their degradation products including adenosine and alpha,beta-methylene-ATP did not inhibit 11beta-HSD2 activity. In contrast, 11beta-HSD2 activity increased almost 2.5-fold after incubation with 2'-methylthio-ATP. This indicates a bidirectional regulation by nucleotides via purinergic receptors. In JEG-3 cells, ATP/ATPgammaS did not alter 11beta-HSD2 promoter activity but reduced 11beta-HSD2 protein and mRNA concentration and half-life, suggesting a posttranscriptional regulation. In conclusion, ATP inhibits cell type specifically via purinergic receptors the expression and activity of the 11beta-HSD2 by a posttranscriptional mechanism.
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PMID:Extracellular ATP determines 11beta-hydroxysteroid dehydrogenase type 2 activity via purinergic receptors. 1625 Dec 42

AMP-activated protein kinase (AMPK) plays a key role in the regulation of energy homeostasis and is activated in response to cellular stress, including hypoxia/ischemia and hyperglycemia. The stress events are accompanied by rapid release of extracellular nucleotides from damaged tissues or activated endothelial cells (EC) and platelets. We demonstrate that extracellular nucleotides (ATP, ADP, and UTP, but not UDP) and adenosine independently induce phosphorylation and activation of AMPK in human umbilical vein EC (HUVEC) by the mechanism that is not linked to changes in AMP:ATP ratio. HUVEC express NTPDases, as well as 5'-nucleotidase; hence, nucleotides can be metabolized to adenosine. However, inhibition of 5'-nucleotidase had no effect on ATP/ADP/UTP-induced phospho- rylation of AMPK, indicating that AMPK activation occurred as a direct response to nucleotides. Nucleotide-evoked phosphorylation of AMPK in HUVEC was mediated by P2Y1, P2Y2, and/or P2Y4 receptors, whereas P2Y6, P2Y11, and P2X receptors were not involved. The nucleotide-induced phosphorylation of AMPK was affected by changes in the concentration of intracellular Ca2+ and by Ca2+/calmodulin-dependent kinase kinase (CaMKK), although most likely it was not dependent on LKB1 kinase. Adenosine-induced phosphorylation of AMPK was not mediated by P1 receptors but required adenosine uptake by equilibrative nucleoside transporters followed by its (intracellular) metabolism to AMP. Moreover, adenosine effect was Ca2+ and CaMKK independent, although probably associated with upstream LKB1. We hypothesize that P2 receptors and adenosine transporters could be novel targets for the pharmacological regulation of AMPK activity and its downstream effects on EC function.
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PMID:Extracellular nucleotides and adenosine independently activate AMP-activated protein kinase in endothelial cells: involvement of P2 receptors and adenosine transporters. 1649 86

Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.
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PMID:Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation. 1654 83

1. Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of relaxin (RLX), known to afford protection against the deleterious effects of cardiac ischemia/reperfusion, given to rats subjected to splanchnic artery occlusion and reperfusion (SAO/R)-induced splanchnic injury. 2. RLX (30 ng kg(-1), 15 min. before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/R. RLX also reduced histopathological changes, leukocyte infiltration (myeloperoxidase) and expression of endothelial cell adhesion molecules in the ileum. RLX counteracted free radical-mediated tissue injury, as judged by significant decrease in the tissue levels of peroxidation and nitration products (malondialdehyde, nitrotyrosine), DNA damage markers (8-hydroxy-2'-deoxyguanosine, poly-ADP-ribosylated DNA) and consumption of tissue antioxidant enzymes (superoxide dismutase). As a result, RLX led to a reduction of ileal cell apoptosis (caspase 3, terminal deoxynucleotidyltransferase-mediated UTP end labeling). The effects of RLX appear specific, as inactivated RLX substituted for the bioactive hormone had no effects. 3. In conclusion, these results show that RLX exerts a clear-cut protective effect in SAO/R-induced splanchnic injury, likely due to endothelial protection, decreased leukocyte recruitment and hindrance of free radical-mediated tissue injury leading to cell death, lethal complications and high mortality rate. Thus, RLX could be used therapeutically in intestinal ischemia.
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PMID:Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion. 1684 43

Our previous study described the neuroprotective effects of catalpol in gerbil ischemic model, in which catalpol was shown to prevent hippocampal neurons from death and ameliorate the cognitive ability of the animals. In the study, we focused on investigating the neuroprotective mechanism of catalpol. Animals were randomly assigned three groups as sham-operated, ischemia-treated with saline and ischemia-treated with catalpol. Transient global ischemia was produced by a 5 min occlusion of the bilateral common carotid arteries. Catalpol was intraperitoneally injected at the dose of 5 mg/kg immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h. Histology as well as immunohistochemistry and TUNEL (the terminal deoxynucleotidyl transferase-mediated UTP nick end label) analysis were performed on serial slices through the dorsal hippocampus after gerbils were sacrificed. The results showed that 5 min transient global ischemia followed by 4 days reperfusion caused significant increases in TUNEL-positive and Bax-positive cells in hippocampal CA1 subfield. Catalpol not only significantly reduced TUNEL-positive and Bax-positive cells but also significantly increased Bcl-2-positive cells. All these suggested that catalpol could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes.
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PMID:Catalpol modulates the expressions of Bcl-2 and Bax and attenuates apoptosis in gerbils after ischemic injury. 1692 64

Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of pea seedling (Latyrus cicera) histaminase, known to afford protection against the deleterious effects of cardiac ischemia/reperfusion, given to rats subjected to SAO/reperfusion-induced splanchnic injury. Histaminase (80 IU kg, 15 min before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/reperfusion. Histaminase also reduced histopathological changes, leukocyte infiltration (myeloperoxidase), and expression of endothelial cell adhesion molecules in the ileum. Histaminase counteracted free radical-mediated tissue injury, as judged by a significant decrease in the plasma and tissue levels of peroxidation and nitration products (oxidized rhodamine, malondialdehyde, nitrotyrosine), DNA damage markers (8-hydroxy-2'-deoxyguanosine, poly-adenosine diphosphate-ribosylated DNA) and consumption of tissue antioxidant enzymes (superoxide dismutase). As a result, histaminase led to a reduction of ileal cell apoptosis (caspase 3, terminal deoxynucleotidyltransferase-mediated UTP end labeling-positive cells). These results show that histaminase exerts a clear-cut protective effect in SAO/reperfusion-induced splanchnic injury, likely caused by oxidative catabolism of proinflammatory histamine and antioxidant effects resulting in hindrance of free radical-mediated tissue injury, endothelial dysfunction, and leukocyte recruitment. Thus, histaminase could be used therapeutically in intestinal ischemia.
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PMID:Beneficial effects of a plant histaminase in a rat model of splanchnic artery occlusion and reperfusion. 1741 24

Ischemic heart disease (IHD) is the main cause of death and a major public health problem in the world. The traditional herbal medicinal formula Guan-Xin-Er-Hao (GXEH) has been used in China and East Asia for the treatment of coronary heart disease, however, the underlying cardioprotection mechanisms remain unclear. To make clear the antiischemic mechanism involved, GXEH was orally administered to 15 healthy volunteers. Heart rates (HR), blood pressure and coronary flow (CF) velocity before and 1 h after a single oral dose of GXEH were observed and compared. It was demonstrated that the oral administration of GXEH increased CF acutely in a dose-dependent manner without modification of systemic hemodynamic parameters. Moreover, the myocardial protection function of GXEH was also experimentally examined in ischemia-reperfusion (I/R) rat models. Apoptosis was measured quantitatively by the terminal transferase UTP nick end-labeling (TUNEL) method and confirmed by caspase-3 activity. The infarct size and TUNEL-positive cells of GXEH-treated group (20 g/kg) were reduced significantly, which was consistent with the decreased caspase-3 activity. These suggest that GXEH protects hearts from ischemia injury by increasing CF and reduces infarct size by inhibiting myocardial apoptosis.
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PMID:Effect of oriental herbal prescription Guan-Xin-Er-Hao on coronary flow in healthy volunteers and antiapoptosis on myocardial ischemia-reperfusion in rat models. 1758 91


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